Myristicin

Last updated
Myristicin
Myristicin.svg
Myristicin-3D-balls.png
Clinical data
Other names3-methoxy-4,5-methylenedioxy-allylbenzene; 5-methoxy-3,4-methylenedioxy-allylbenzene
Dependence
liability
Low/None / Not Typical
Addiction
liability
Low
Routes of
administration
Oral
Legal status
Legal status
  • In general: uncontrolled, could be illegal in the UK under the Psychoactive Substances Act 2016 if it's sold for human consumption or synthetized for recreational use.
Identifiers
  • 7-Allyl-5-methoxy-1,3-benzodioxole
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.009.225 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C11H12O3
Molar mass 192.214 g·mol−1
3D model (JSmol)
  • O1c2cc(cc(OC)c2OC1)C\C=C
  • InChI=1S/C11H12O3/c1-3-4-8-5-9(12-2)11-10(6-8)13-7-14-11/h3,5-6H,1,4,7H2,2H3 Yes check.svgY
  • Key:BNWJOHGLIBDBOB-UHFFFAOYSA-N Yes check.svgY
   (verify)

Myristicin is a naturally occurring compound found in common herbs and spices, such as nutmeg. [1] [2] It is an insecticide, and has been shown to enhance the effectiveness of other insecticides. [1] [3]

Contents

When ingested, myristicin may produce hallucinogenic effects, [1] [4] and can be converted to MMDMA in controlled chemical synthesis. [5] It interacts with many enzymes and signaling pathways in the body, [6] [7] and may have dose-dependent cytotoxicity in living cells. [6] Myristicin is listed in the Hazardous Substances Data Bank. [1]

Uses

Isolated myristicin has proven an effective insecticide against many agricultural pests, including Aedes aegypti mosquito larvae, Spilosoma obliqua (hairy caterpillars), [8] Epilachna varivestis (Mexican bean beetles), Acyrthosiphon pisum (pea aphids), mites, and Drosophila melanogaster (fruit flies). Myristicin was shown to be an effective repellant, and to cause mortality via direct and systemic exposure. It also displayed a synergistic effect when administered to insects in combination with existing insecticides. [3]

The structure of myristicin closely resembles that of amphetamine compounds, and it is capable of producing psychotropic effects similar to MDMA compounds. [1] Because of this, it can be used in synthetic synthesis to create amphetamine derivatives, and create designer drugs like MMDMA that are similar in structure and effect to MDMA. [5] Out of the common spices that contain myristicin, nutmeg has a high relative concentration of the compound, [2] and therefore is used to exploit the effects of myristicin. [1] [2]

Furthermore, myristicin interferes with multiple signaling pathways and enzyme processes in the body. [1] [6] [7]

Sources of myristicin

Myristicin can be found in the essential oil of nutmeg, black pepper, kawakawa, [9] and many members of the Umbelliferae family, including anise, carrots, parsley, celery, dill, [10] and parsnip. [3]

Trace amounts have also been isolated from a variety of plant species including Ridolfia segetum (harvest fennel), species of the Oenanthe genus (water dropworts), species of the Lamiaceae family (mint, sage, or deadnettle families), Cinnamomum glanduliferum (Nepal camphor tree), [11] and Piper mullesua ("Hill Pepper"). [8]

Depending on the conditions of growth and storage of the plant, a high quality nutmeg ( Myristica fragrans) seed can contain up to 13 mg of myristicin per 1 gram. [12]

Physiological effects

Psychoactive effects

At a minimum dose of about 5 g of nutmeg powder, symptoms of nutmeg intoxication can begin to emerge. [10] Nutmeg intoxication may produce dizziness, drowsiness, and confusion, although in higher amounts, it may have effects similar to other deliriants due to its hallucinogenic effects. [1] [13]

Pharmacology

Myristicin is additionally known to be a weak inhibitor of monoamine oxidase (MAO), an enzyme in humans that metabolizes neurotransmitters (e.g., serotonin, dopamine, epinephrine, and norepinephrine). It lacks the basic nitrogen atom that is typical of MAO inhibitors (MAOIs), potentially explaining a weaker inhibitory effect. [14]

While smaller concentrations of MAOIs may not cause problems, there are additional warnings regarding drug interactions. Those taking antidepressants that are MAOIs (such as phenelzine, isocarboxazid, tranylcypromine or selegiline [15] ) or taking selective serotonin re-uptake inhibiting (SSRI) antidepressants should avoid essential oils rich in myristicin, such as that of nutmeg or anise. [16]

Metabolites

Brief overview of synthesis and metabolism Myristicin to MMDMA Synthesis.svg
Brief overview of synthesis and metabolism

Metabolism of myristicin yields 3-methoxycatechol [1] and enzymatically forms 5-allyl-1-methoxy-2,3-dihydroxybenzene (oxidation of the methylenedioxy group). Myristicin is also formed into demethylenylmyristicin, dihydroxymyristicin, and elemicin is formed into O-demethylelemicin, O-demethyldihydroxyelemicin, and safrole. [1] [ citation needed ]

Chemistry

Structural comparison of myristicin, amphetamine and derivatives Amphetamine derivative and myristicin structures.svg
Structural comparison of myristicin, amphetamine and derivatives

With a chemical structure resembling amphetamines and other precursors, myristicin can also be used to synthesize illicit hallucinogenic drugs. Under controlled conditions, myristicin isolated from nutmeg oil can be converted into MMDMA, a synthetic "designer drug" amphetamine derivative that is less potent than MDMA but produces comparable stimulant and hallucinogenic effects. [5]

Myristicin is insoluble in water, and soluble in ethanol, ether, and benzene. [1]

Toxicity

In laboratory studies, myristicin is cytotoxic. [1] Specifically, it stimulates cytochrome c release, which activates caspase cascades and induces early apoptosis in the cells. [6] Myristicin has also been shown to inhibit cytochrome P450 enzymes, which are responsible for metabolizing a variety of substrates including hormones and toxins, allowing these substrates to accumulate. [1] [7]

The effects of nutmeg consumed in large doses are attributed mostly to myristicin, where 1–7 hours following ingestion, symptoms include disorientation, giddiness, stupor, and stimulation of the central nervous system leading to euphoria. [1] [2] Also occurring are mild to intense hallucinations (similar to deliriants, walls and ceiling glitching or breathing), disorientation to time and surroundings, disassociation, feelings of levitation, loss of consciousness, tachycardia, weak pulse, anxiety, and hypertension. [1] Symptoms of nutmeg intoxication further include nausea, abdominal pain, vomiting, minor to severe muscle spasms (severe in extreme overdose), headache, dryness of mouth, mydriasis or miosis, hypotension, shock, and potentially death. [1] [2] [4]

Myristicin poisoning can be detected by testing levels of myristicin in the blood. [17] There are no known antidotes for myristicin poisoning, and treatment focuses on symptom management and potential sedation in cases of extreme delirium or aggravation. [1] [18]

Related Research Articles

<span class="mw-page-title-main">Monoamine oxidase inhibitor</span> Type of medication

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.

<span class="mw-page-title-main">Serotonin syndrome</span> Symptoms caused by an excess of serotonin in the central nervous system

Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild cases include high blood pressure and a fast heart rate; usually without a fever. Symptoms in moderate cases include high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhea. In severe cases, body temperature can increase to greater than 41.1 °C (106.0 °F). Complications may include seizures and extensive muscle breakdown.

<span class="mw-page-title-main">Psychopharmacology</span> Study of the effects of psychoactive drugs

Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.

α-Methyltryptamine Chemical compound

α-Methyltryptamine is a psychedelic, stimulant, and entactogen drug of the tryptamine class. It was originally developed as an antidepressant by workers at Upjohn in the 1960s, and was used briefly as an antidepressant in Russia under the trade name Indopan before being discontinued.

<span class="mw-page-title-main">Phenelzine</span> Antidepressant

Phenelzine, sold under the brand name Nardil, among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is primarily used as an antidepressant and anxiolytic. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use.

<span class="mw-page-title-main">Tranylcypromine</span> Irreversible non-selective MAO inhibitor Antidepressant drug

Tranylcypromine, sold under the brand name Parnate among others, is a monoamine oxidase inhibitor (MAOI). More specifically, tranylcypromine acts as nonselective and irreversible inhibitor of the enzyme monoamine oxidase (MAO). It is used as an antidepressant and anxiolytic agent in the clinical treatment of mood and anxiety disorders, respectively.

5-Methoxy-<i>N</i>,<i>N</i>-diisopropyltryptamine Psychedelic tryptamine

5-Methoxy-N,N-diisopropyltryptamine is a psychedelic tryptamine and the methoxy derivative of diisopropyltryptamine (DiPT).

α-Ethyltryptamine Chemical compound

α-Ethyltryptamine, also known as etryptamine, is a psychedelic, stimulant, and entactogenic drug of the tryptamine class. It was originally developed and marketed as an antidepressant under the brand name Monase by Upjohn in the 1960s.

<i>para</i>-Methoxyamphetamine Chemical compound

para-Methoxyamphetamine (PMA), also known as 4-methoxyamphetamine (4-MA), is a designer drug of the amphetamine class with serotonergic effects. Unlike other similar drugs of this family, PMA does not produce stimulant, euphoriant, or entactogen effects, and behaves more like an antidepressant in comparison, though it does have some psychedelic properties.

<span class="mw-page-title-main">Harmala alkaloid</span> Group of chemical compounds

Harmala alkaloids are several alkaloids that increase effects of reward system neurotransmitter dopamine by acting as monoamine oxidase inhibitors (MAOIs). These alkaloids are found in the seeds of Peganum harmala, as well as leaves of tobacco. The alkaloids include harmine, harmaline, harmalol, and their derivatives, which have similar chemical structures, hence the name "harmala alkaloids". These alkaloids are of interest for their use in Amazonian shamanism, where they are derived from other plants. Harmine, once known as telepathine and banisterine, is a naturally occurring beta-carboline alkaloid that is structurally related to harmaline, and also found in the vine Banisteriopsis caapi. Tetrahydroharmine is also found in B. caapi and P. harmala. Dr. Alexander Shulgin has suggested that harmine may be a breakdown product of harmaline. Harmine and harmaline are reversible inhibitors of monoamine oxidase A (RIMAs). They can stimulate the central nervous system by inhibiting the metabolism of monoamine compounds such as serotonin and norepinephrine.

<span class="mw-page-title-main">Harmaline</span> Chemical compound

Harmaline is a fluorescent indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the partly hydrogenated form of harmine.

<span class="mw-page-title-main">Deliriant</span> Class of psychoactive drugs

Deliriants are a subclass of hallucinogen. The term was coined in the early 1980s to distinguish these drugs from psychedelics and dissociatives such as LSD and ketamine, respectively, due to their primary effect of causing delirium, as opposed to the more lucid and less disturbed states produced by other types of hallucinogens. The term generally refers to anticholinergic drugs, which are substances that inhibit the function of the neurotransmitter acetylcholine. Common examples of deliriants include plants of the genera Datura and Brugmansia as well as higher than recommended dosages of diphenhydramine (Benadryl). A number of plant deliriants such as that of the Solanaceae family, particularly in the Americas have been used by some indigenous cultures to reach delirious and altered states for traditions or rituals, such as rites of passage, divination or communicating with the ancestors. Despite their long history of use, deliriants are the least-studied class of hallucinogens in terms of their behavioral and neurological effects.

<span class="mw-page-title-main">Dopaminergic</span> Substance related to dopamine functions

Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that release dopamine or express dopamine receptors) can also be said to have dopaminergic effects, two prominent examples being opioids, which enhance dopamine release indirectly in the reward pathways, and some substituted amphetamines, which enhance dopamine release directly by binding to and inhibiting VMAT2.

<span class="mw-page-title-main">Moclobemide</span> Antidepressant

Moclobemide, sold under the brand names Amira, Aurorix, Clobemix, Depnil and Manerix among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety. It is not approved for use in the United States, but is approved in other Western countries such as Canada, the UK and Australia. It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.

A drug with psychotomimetic actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to only hallucinations. Psychotomimesis is the onset of psychotic symptoms following the administration of such a drug.

<span class="mw-page-title-main">MMDMA</span> Chemical compound

5-Methoxy-3,4-methylenedioxymethamphetamine is a designer drug of the substituted methylenedioxyphenethylamine (MDxx) class. Little is known about its effects and it has not been formally studied in animals.

<i>para</i>-Methoxy-<i>N</i>-methylamphetamine Stimulant and psychedelic designer drug

para-Methoxy-N-methylamphetamine, chemically known as methyl-MA, 4-methoxy-N-methylamphetamine, 4-MMA) or is a stimulant and psychedelic drug closely related to the amphetamine-class serotonergic drug para-methoxyamphetamine (PMA). PMMA is the 4-methoxy analog of methamphetamine. Little is known about the pharmacological properties, metabolism, and toxicity of PMMA; because of its structural similarity to PMA, which has known toxicity in humans, it is thought to have considerable potential to cause harmful side effects or death in overdose. In the early 2010s, a number of deaths in users of the drug MDMA were linked to misrepresented tablets and capsules of PMMA.

An adrenergic storm is a sudden and dramatic increase in serum levels of the catecholamines adrenaline and noradrenaline, with a less significant increase in dopamine transmission. It is a life-threatening condition because of extreme tachycardia and hypertension, and is especially dire for those with prior heart problems. If treatment is prompt, prognosis is good; typically large amounts of diazepam or other benzodiazepines are administered alongside beta blockers. Beta blockers are contraindicated in some patients, so other anti-hypertensive medication such as clonidine may be used. Antipsychotics are also used to treat the most severe psychiatric reactions such as psychosis, paranoia or terror, after their use was formerly discouraged because of their potential to prolong the QT interval; however, more recent research performed since 2019 has revealed that this and other severe side effects are rare and their occurrence does not warrant banning antipsychotics from the treatment of adrenergic crises for which they can be extremely useful.

<span class="mw-page-title-main">Amiflamine</span> Chemical compound

Amiflamine (FLA-336) is a reversible inhibitor of monoamine oxidase A (MAO-A), thereby being a RIMA, and, to a lesser extent, semicarbazide-sensitive amine oxidase (SSAO), as well as a serotonin releasing agent (SRA). It is a derivative of the phenethylamine and amphetamine chemical classes. The (+)-enantiomer is the active stereoisomer.

Amphetamine type stimulants (ATS) are a group of synthetic drugs that are chemical derivatives of the parent compound alpha-methylphenethylamine, also known as amphetamine. Common ATS includes amphetamine, methamphetamine, ephedrine, pseudoephedrine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxyethylamphetamine (MDEA). ATS when used illicitly has street names including ice, meth, crystal, crank, bennies, and speed. Within the group of amphetamine-type stimulants, there are also prescription drugs including mixed amphetamine salts, dextroamphetamine, and lisdexamfetamine.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 "Myristicin". PubChem, US National Library of Medicine. 13 May 2023. Retrieved 14 May 2023.
  2. 1 2 3 4 5 "Nutmeg". Drugs.com. 21 November 2022. Retrieved 14 May 2023.
  3. 1 2 3 Lichtenstein EP, Casida JE (1963). "Naturally Occurring Insecticides, Myristicin, an Insecticide and Synergist Occurring Naturally in the Edible Parts of Parsnips". Journal of Agricultural and Food Chemistry. 11 (5): 410–415. doi:10.1021/jf60129a017.
  4. 1 2 Stein U, Greyer H, Hentschel H (April 2001). "Nutmeg (myristicin) poisoning--report on a fatal case and a series of cases recorded by a poison information centre". Forensic Science International. 118 (1): 87–90. doi:10.1016/s0379-0738(00)00369-8. PMID   11343860.
  5. 1 2 3 4 Clark CR, DeRuiter J, Noggle FT (1996-01-01). "Analysis of 1-(3-Methoxy-4,5-Methylenedioxyphenyl)-2-Propanamine(MMDA)Derivatives Synthesized from Nutmeg Oil and 3-Methoxy-4,5-Methylenedioxybenzaldehyde". Journal of Chromatographic Science. 34 (1): 34–42. doi: 10.1093/chromsci/34.1.34 .
  6. 1 2 3 4 Lee BK, Kim JH, Jung JW, Choi JW, Han ES, Lee SH, et al. (May 2005). "Myristicin-induced neurotoxicity in human neuroblastoma SK-N-SH cells". Toxicology Letters. 157 (1): 49–56. doi:10.1016/j.toxlet.2005.01.012. PMID   15795093.
  7. 1 2 3 Yang AH, He X, Chen JX, He LN, Jin CH, Wang LL, et al. (July 2015). "Identification and characterization of reactive metabolites in myristicin-mediated mechanism-based inhibition of CYP1A2". Chemico-Biological Interactions. 237: 133–40. doi:10.1016/j.cbi.2015.06.018. PMID   26091900.
  8. 1 2 Srivastava S, Gupta MM, Prajapati V, Tripathi AK, Kumar S (2001). "Insecticidal Activity of Myristicin from Piper mullesua". Pharmaceutical Biology. 39 (3): 226–229. doi:10.1076/phbi.39.3.226.5933. S2CID   83947896.
  9. Vennell, Robert (2019). The Meaning of Trees. Auckland: HarperCollins Publishers Ltd. pp. 24–27. ISBN   978-1-77554-130-1. LCCN   2019403535. OCLC   1088638115. Wikidata   Q118646408.
  10. 1 2 Rahman NA, Fazilah A, Effarizah ME (2015). "Toxicity of Nutmeg (Myristicin): A Review". International Journal on Advanced Science, Engineering and Information Technology. 5 (3): 212–215. CiteSeerX   10.1.1.920.6379 . doi: 10.18517/ijaseit.5.3.518 .
  11. Shulgin AT (April 1966). "Possible implication of myristicin as a psychotropic substance". Nature. 210 (5034): 380–4. Bibcode:1966Natur.210..380S. doi:10.1038/210380a0. PMID   5336379. S2CID   4189608.
  12. Nowak J, Woźniakiewicz M, Gładysz M, Sowa A, Kościelniak P (2015). "Development of Advance Extraction Methods for the Extraction of Myristicin from Myristica fragrans". Food Analytical Methods. 9 (5): 1246–1253. doi: 10.1007/s12161-015-0300-x .
  13. Roeters van Lennep JE, Schuit SC, van Bruchem-Visser RL, Özcan B (January 2015). "Unintentional nutmeg autointoxication". The Netherlands Journal of Medicine. 73 (1): 46–48. PMID   26219944.
  14. Truitt EB, Duritz G, Ebersberger EM (March 1963). "Evidence of monoamine oxidase inhibition by myristicin and nutmeg". Proceedings of the Society for Experimental Biology and Medicine. 112 (3): 647–50. doi:10.3181/00379727-112-28128. PMID   13994372. S2CID   44996415.
  15. "Monoamine oxidase inhibitors (MAOIs)". Mayo Clinic. 12 September 2019.
  16. Tisserand R, Young R (2014). "Kinetics and dosing". Essential Oil Safety. pp. 39–67. doi:10.1016/b978-0-443-06241-4.00004-7. ISBN   978-0-443-06241-4.
  17. Baselt RC (2008). Disposition of toxic drugs and chemicals in man (8th ed.). Foster City, Ca: Biomedical Publications. ISBN   978-0-9626523-7-0. OCLC   243548756.[ page needed ]
  18. Demetriades AK, Wallman PD, McGuiness A, Gavalas MC (March 2005). "Low cost, high risk: accidental nutmeg intoxication". Emergency Medicine Journal. 22 (3): 223–5. doi:10.1136/emj.2002.004168. PMC   1726685 . PMID   15735280.